Cycle 1 and further cycles

Drug

Dose

Route

Day

DOXOrubicin Liposomal

40 mg/m2 *

IV infusion

1

*It is the consensus of the reference committee that the original dose of liposomal doxorubicin (50 mg/m2) used in the clinical trial be reduced to 40 mg/m2 as the higher dose is undeliverable in clinical practice due to toxicity.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

DOXOrubicin Liposomal

40 mg/m2 (IV infusion)

in 250 mL glucose 5%

at a rate of 1 mg/min for the first cycle then over 60 minutes for subsequent cycles

It is the consensus of the reference committee that the original dose of liposomal doxorubicin (50 mg/m2) used in the clinical trial be reduced to 40 mg/m2 as the higher dose is undeliverable in clinical practice due to toxicity.

Cycle 1 and further cycles

Drug

Dose

Route

Day

DOXOrubicin Liposomal

40 mg/m2 *

IV infusion

1

*It is the consensus of the reference committee that the original dose of liposomal doxorubicin (50 mg/m2) used in the clinical trial be reduced to 40 mg/m2 as the higher dose is undeliverable in clinical practice due to toxicity.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1

Metoclopramide

10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)

DOXOrubicin Liposomal

40 mg/m2 (IV infusion)

in 250 mL glucose 5%

at a rate of 1 mg/min for the first cycle then over 60 minutes for subsequent cycles

It is the consensus of the reference committee that the original dose of liposomal doxorubicin (50 mg/m2) used in the clinical trial be reduced to 40 mg/m2 as the higher dose is undeliverable in clinical practice due to toxicity.

The total cumulative lifetime dose of pegylated liposomal doxorubicin has not been defined.

Monitoring of cardiac function is recommended when lifetime cumulative dose of liposomal doxorubicin exceeds 700 mg/m2 or where a lifetime cumulative dose of 450 mg/m2 of other anthracyclines has been administered prior to liposomal doxorubicin.

Assess patient for risk of cardiotoxicity. Routine surveillance is not indicated in the absence of risk factors, symptoms or clinical evidence of cardiac toxicity.

Monitor patient for presence of hand-foot syndrome (palmar-plantar erythrodysaesthesia). If present patient may require an interruption in treatment. For further information see Dose modifications section below.

Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the antineoplastic regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information and reference committee consensus. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: all dose reductions are calculated as a percentage of the starting dose

Haematological toxicity

ANC x 109/L (pre-treatment blood test)

1.0 to less than 1.5

Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well

0.5 to less than 1.0

Delay treatment until recovery

less than 0.5

Delay treatment until recovery and reduce liposomal doxorubicin by 25% for subsequent cycles

Febrile neutropenia

Delay treatment until recovery and reduce liposomal doxorubicin by 25% for subsequent cycles

Platelets x 109/L (pre-treatment blood test)

75 to less than 100

The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines.

50 to less than 75

Delay treatment until recovery

less than 50

Delay treatment until recovery and reduce liposomal doxorubicin by 25% for subsequent cycles

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.

Digoxin

Antineoplastic agents can damage the lining of the intestine; affecting the absorption of digoxin

Monitor digoxin serum levels; adjust digoxin dosage as appropriate

Antiepileptics

Both altered antiepileptic and antineoplastic levels may occur, possibly leading to loss of efficacy or toxicity

Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the antineoplastic therapy

Diminished response to vaccines and increased risk of infection with live vaccines

Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

Discharge information

Antiemetics

Patient information

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)

Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, radiotherapy to the head, neck or oesophagus, and high dose chemotherapy followed by a blood and marrow transplant (BMT).

Bilateral erythema, tenderness, pain, swelling, tingling, numbness, pruritus, dry rash, or moist desquamation and ulceration of the palms and soles. It is also known as hand-foot syndrome (HFS). Symptoms appear to be dose dependent and palms are affected more than soles.

Irregular or absent periods, hot flushes, mood swings, sleep disturbance, night sweats, vaginal dryness, decreased libido and dyspareunia. This is caused by ovarian failure and may be temporary or permanent.

Cardiotoxicity

Anthracyclines are the most frequently implicated antineoplastic agents associated with cardiotoxicity, which typically manifests as a reduction in left ventricular ejection fraction (LVEF), cardiomyopathy, or symptomatic CHF. Anthracycline induced cardiotoxicity has been categorised into acute, early-onset chronic progressive and late-onset chronic progressive and is usually not reversible. The risk of clinical cardiotoxicity increases with a number of risk factors including higher total cumulative doses.

Liposomal doxorubicin at a dose of 50 mg/m2 is equally effective as first line therapy of metastatic breast cancer as doxorubicin 60 mg/m2 with the advantage of reduced cardiac toxicity.rCardiac toxicity remains at < 10% with cumulative doses up to 600 mg/m2 in anthracycline naive patients. However, It is important to note that liposomal doxorubicin is not effective in anthracycline resistant diseaser and shows minimal activity in taxane refractory patients. A randomised controlled trial of liposomal doxorubicin compared to vinorelbine or mitomycin C and vinblastine, in women with taxane-refractory advanced breast cancer, showed minimal activity in either arm with an 8-10% response rate.r

Toxicity

In both groups 24% of patients discontinued due to toxicity (adverse event or cardiac toxicity). In the liposomal doxorubicin group 22% discontinued due to an adverse event and 2.4% due to cardiac toxicity, whereas among the doxorubicin group 9.4% discontinued due to an adverse event and 14% due to cardiac toxicity. Palmar-plantar erythrodysesthesia (PPE) was the most common adverse event 48% (grade 3 = 17%) with the liposomal doxorubicin group.r

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